Objective: Intuitively malignancies enlarge because net protein synthesis exceeds the rate of breakdown. The aim of this study was to assess whether this kinetic imbalance is related to an increase in protein synthesis or an inhibition of protein breakdown. Methods: Five patients (age 59+3 yrs) with adenocarcinoma of the colon undergoing colonoscopy were studied. Tissue protein synthesis and breakdown rates were measured in vivo for both segments of colon cancer and adjacent normal appearing colonic mucosa utilizing a primed, continuous infusion of l"C leucine with tissue biopsy and quantitation of regional blood flow using laser Doppler flowmetry. A Student's paired "t" test was employed for statistical comparison. Conclusions: These results illustrate that human colon cancers grow in vivo due to increases in net protein synthesis. Furthermore, increases in regional blood flow limit the rate of tissue protein breakdown of colon cancer thus contributing to growth of the malignancy. These findings support the contention that therapeutic strategies aimed at negating this inherent increase in protein synthesis and/or limiting blood flow may be efficacious in inhibiting the growth of malignancies. This methodology may also provide an index for quantitating the effectiveness of future therapies aimed at reducing tumor growth on an individual patient basis.